Knowledge of the three dimensional structure of a protein is often necessary in order fully to elucidate its biological function and its interaction with other proteins, and with non-protein cofactors, in a physiological pathway. Knowledge of a protein's 3D structure is critical to the rational design of small chemical entities capable of interacting with the protein with high affinity, a process used both for creation and for optimization of pharmaceutical compounds intended for ultimate use in the clinic.
Although solution phase NMR spectroscopy has shown promise in elucidating protein 3D structure, its use is circumscribed by various technical limitations, and X-ray crystallography remains the principal means by which three dimensional protein structures are determined at the atomic level.
Yet crystallization of proteins remains an inexact and cumbersome art.
Typically, a protein desired to be crystallized is subjected to a wide variety of environmental conditions, including a wide range of solution chemistries, either serially or in a highly parallel series of assays. The large number of assays demands a commensurately large quantity of protein. Positive results occur episodically, and often only after weeks of incubation. Even when a positive result is obtained in the form of a crystal, preparing and mounting the crystal on an x-ray machine can be an arduous, time-consuming process that often results in crystal degradation or even loss.
Thus, there exists a need in the art for a simple, rapid, versatile method of producing protein crystals that neither requires multiple assays, a large amount of protein, nor difficult crystal manipulation methods.